Manipulation of mechanical ventilatory constraint during moderate intensity exercise does not influence dyspnoea in healthy older men and women.

KEY POINTS: The perceived intensity of exertional breathlessness (i.e. dyspnoea) is higher in older women than in older men, possibly as a result of sex-differences in respiratory system morphology. During exercise at a given absolute intensity or minute ventilation, older women have a greater degree of mechanical ventilatory constraint (i.e. work of breathing and expiratory flow limitation) than their male counterparts, which may lead to a greater perceived intensity of dyspnoea. Using a single-blind randomized study design, we experimentally manipulated the magnitude of mechanical ventilatory constraint during moderate-intensity exercise at ventilatory threshold in healthy older men and women. We found that changes in the magnitude of mechanical ventilatory constraint within the physiological range had no effect on dyspnoea in healthy older adults. When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea. ABSTRACT: We aimed to determine the effect of manipulating mechanical ventilatory constraint during submaximal exercise on dyspnoea in older men and women. Eighteen healthy subjects (aged 60-80 years; nine men and nine women) completed two days of testing. On day 1, subjects were assessed for pulmonary function and performed a maximal incremental cycle exercise test. On day 2, subjects performed three 6-min bouts of cycling at ventilatory threshold, in a single-blind randomized manner, while breathing: (i) normoxic helium-oxygen (HEL) to reduce the work of breathing (Wb ) and alleviate expiratory flow limitation (EFL); (ii) through an inspiratory resistance (RES) of ∼5 cmH2 O L-1  s-1 to increase Wb ; and (iii) ambient air as a control (CON). Oesophageal pressure, diaphragm electromyography, and sensory responses (category-ratio 10 Borg scale) were monitored throughout exercise. During the HEL condition, there was a significant decrease in Wb (men: -21 ± 6%, women: -17 ± 10%) relative to CON (both P < 0.01). Moreover, if EFL was present during CON (four men and five women), it was alleviated during HEL. Conversely, during the RES condition, Wb (men: 42 ± 19%, women: 50 ± 16%) significantly increased relative to CON (both P < 0.01). There was no main effect of sex on Wb (P = 0.59). Across conditions, women reported significantly higher dyspnoea intensity than men (2.9 ± 0.9 vs. 1.9 ± 0.8 Borg scale units, P < 0.05). Despite significant differences in the degree of mechanical ventilatory constraint between conditions, the intensity of dyspnoea was unaffected, independent of sex (P = 0.46). When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea.

Analysis of maximal expiratory flow-volume curves in adult survivors of preterm birth.

Adult survivors of very preterm (≤32 wk gestational age) birth without (PRE) and with bronchopulmonary dysplasia (BPD) have variable degrees of airflow obstruction at rest. Assessment of the shape of the maximal expiratory flow-volume (MEFV) curve in PRE and BPD may provide information concerning their unique pattern of airflow obstruction. The purposes of the present study were to 1) quantitatively assess the shape of the MEFV curve in PRE, BPD, and healthy adults born at full-term (CON), 2) identify where along the MEFV curve differences in shape existed between groups, and 3) determine the association between an index of MEFV curve shape and characteristics of preterm birth (i.e., gestational age, mass at birth, duration of oxygen therapy) in PRE and BPD. To do so, we calculated the average slope ratio (SR) throughout the effort-independent portion of the MEFV curve and at increments of 5% of forced vital capacity (FVC) between 20 and 80% of FVC in PRE (n = 19), BPD (n = 25), and CON (n = 20). We found that average SR was significantly higher in PRE (1.34 ± 0.35) and BPD (1.33 ± 0.45) compared with CON (1.03 ± 0.22; both P < 0.05) but similar between PRE and BPD (P = 0.99). Differences in SR between groups occurred early in expiration (i.e., 20-30% of FVC). There was no association between SR and characteristics of preterm birth in PRE and BPD groups (all P > 0.05). The mechanism(s) of increased SR during early expiration in PRE/BPD relative to CON is unknown but may be due to differences in the structural and mechanical properties of the airways.

Modelling the effects of age and sex on the resistive and viscoelastic components of the work of breathing during exercise.

NEW FINDINGS: What is the central question of this study? What is the effect of age and sex on the resistive and viscoelastic components of work of breathing (Wb ) during exercise? What is the main finding and its importance? The resistive and viscoelastic components of Wb were higher in older adults, regardless of sex. The resistive, but not viscoelastic, component of Wb was higher in females than in males, regardless of age. These findings contribute to improving our understanding of the effects of ageing and sex on the mechanical ventilatory response to exercise. ABSTRACT: Healthy ageing and biological sex each affect the work of breathing (Wb ) for a given minute ventilation ( V̇E ). Age-related structural changes to the respiratory system lead to an increase in both the resistive and viscoelastic components of Wb ; however, it is unclear whether healthy ageing differentially alters the mechanics of breathing in males and females. We analysed data from 22 older (60-80 years, n = 12 females) and 22 younger (20-30 years, n = 11 females) males and females that underwent an incremental cycle exercise test to exhaustion. V̇E and Wb were assessed at rest and throughout exercise. Wb - V̇E data for each participant were fitted to a non-linear equation (i.e. Wb  = a V̇E3 + b V̇E2 ) that partitions Wb into resistive (i.e. a V̇E3 ) and viscoelastic (i.e. b V̇E2 ) components. We then modelled the effects of healthy ageing and biological sex on each component of Wb . Overall, the model fit was excellent (r2 : 0.99 ± 0.01). There was a significant main effect of age and sex on the resistive component of Wb (both P < 0.05), and a significant main effect of age (P < 0.001), but not sex (P = 0.309), on the viscoelastic component of Wb . No significant interactions between age and sex on a V̇E3 or b V̇E2 were noted (both P > 0.05). Our findings indicate that during exercise: (i) the higher total Wb in females relative to males is due to a higher resistive, but not viscoelastic, component of Wb , and (ii) regardless of sex, the higher Wb in older adults relative to younger adults is due to higher resistive and viscoelastic components of Wb .

Sex Differences in the Pulmonary System Influence the Integrative Response to Exercise.

Healthy women have proportionally smaller lungs and airways compared with height-matched men. These anatomical sex-based differences result in greater mechanical ventilatory constraints and may influence the integrative response to exercise. Our review will examine this hypothesis in healthy humans in the context of dynamic whole-body exercise.

Neurophysiological mechanisms of exertional dyspnoea in fibrotic interstitial lung disease.

Our understanding of the mechanisms of dyspnoea in fibrotic interstitial lung disease (ILD) is incomplete. The aims of this study were two-fold: 1) to determine whether dyspnoea intensity is better predicted by neural respiratory drive (NRD) or neuromechanical uncoupling (NMU) of the respiratory system in fibrotic ILD, and 2) to examine the effect of breathing 60% oxygen on NRD, NMU and dyspnoea ratings.Fourteen patients with fibrotic ILD were included. Visit 1 comprised a familiarisation incremental cycle exercise test, Visit 2 comprised a normoxic incremental cycling test to address Aim 1, and Visits 3 and 4 consisted of constant-load cycling while breathing room air or 60% oxygen to address Aim 2. Diaphragmatic electromyography (EMGdi) was used as a surrogate of NRD. NMU was calculated as the ratio between EMGdi (%max) and tidal volume (%vital capacity).On adjusted analysis, NMU and its constituents were all significantly associated with dyspnoea ratings during incremental cycling, with EMGdi having the strongest correlation. The between-treatment change in dyspnoea ratings during constant load cycling was only correlated with change in exercise endurance time and NMU.Dyspnoea more strongly reflected the level of EMGdi than NMU in fibrotic ILD. However, the improvement in dyspnoea with 60% oxygen was better predicted by improvements in NMU.

Exercise-induced quadriceps muscle fatigue in men and women: effects of arterial oxygen content and respiratory muscle work.

KEY POINTS: High work of breathing and exercise-induced arterial hypoxaemia (EIAH) can decrease O2 delivery and exacerbate exercise-induced quadriceps fatigue in healthy men. Women have a higher work of breathing during exercise, dedicate a greater fraction of whole-body V̇O2 towards their respiratory muscles and develop EIAH. Despite a greater reduction in men's work of breathing, the attenuation of quadriceps fatigue was similar between the sexes. The degree of EIAH was similar between sexes, and regardless of sex, those who developed the greatest hypoxaemia during exercise demonstrated the most attenuation of quadriceps fatigue. Based on our previous finding that women have a greater relative oxygen cost of breathing, women appear to be especially susceptible to work of breathing-related changes in quadriceps muscle fatigue. ABSTRACT: Reducing the work of breathing or eliminating exercise-induced arterial hypoxaemia (EIAH) during exercise decreases the severity of quadriceps fatigue in men. Women have a greater work of breathing during exercise, dedicate a greater fraction of whole-body V̇O2 towards their respiratory muscles, and demonstrate EIAH, suggesting women may be especially susceptible to quadriceps fatigue. Healthy subjects (8 male, 8 female) completed three constant load exercise tests over 4 days. During the first (control) test, subjects exercised at ∼85% of maximum while arterial blood gases and work of breathing were assessed. Subsequent constant load exercise tests were iso-time and iso-work rate, but with EIAH prevented by inspiring hyperoxic gas or work of breathing reduced via a proportional assist ventilator (PAV). Quadriceps fatigue was assessed by measuring force in response to femoral nerve stimulation. For both sexes, quadriceps force was equally reduced after the control trial (-27 ± 2% baseline) and was attenuated with hyperoxia and PAV (-18 ± 1 and -17 ± 2% baseline, P < 0.01, respectively), with no sex difference. EIAH was similar between the sexes, and regardless of sex, subjects with the lowest oxyhaemoglobin saturation during the control test had the greatest quadriceps fatigue attenuation with hyperoxia (r2  = 0.79, P < 0.0001). For the PAV trial, despite reducing the work of breathing to a greater degree in men (men: 60 ± 5, women: 75 ± 6% control, P < 0.05), the attenuation of quadriceps fatigue was similar between the sexes (36 ± 4 vs. 37 ± 7%). Owing to a greater relative V̇O2 of the respiratory muscles in women, less of a change in work of breathing is needed to reduce quadriceps fatigue.

Effects of respiratory muscle work on respiratory and locomotor blood flow during exercise.

NEW FINDINGS: What is the central question of this study? Does manipulation of the work of breathing during high-intensity exercise alter respiratory and locomotor muscle blood flow? What is the main finding and its importance? We found that when the work of breathing was reduced during exercise, respiratory muscle blood flow decreased, while locomotor muscle blood flow increased. Conversely, when the work of breathing was increased, respiratory muscle blood flow increased, while locomotor muscle blood flow decreased. Our findings support the theory of a competitive relationship between locomotor and respiratory muscles during intense exercise. Manipulation of the work of breathing (WOB) during near-maximal exercise influences leg blood flow, but the effects on respiratory muscle blood flow are equivocal. We sought to assess leg and respiratory muscle blood flow simultaneously during intense exercise while manipulating WOB. Our hypotheses were as follows: (i) increasing the WOB would increase respiratory muscle blood flow and decrease leg blood flow; and (ii) decreasing the WOB would decrease respiratory muscle blood flow and increase leg blood flow. Eight healthy subjects (n = 5 men, n = 3 women) performed a maximal cycle test (day 1) and a series of constant-load exercise trials at 90% of peak work rate (day 2). On day 2, WOB was assessed with oesophageal balloon catheters and was increased (via resistors), decreased (via proportional assist ventilation) or unchanged (control) during the trials. Blood flow was assessed using near-infrared spectroscopy optodes placed over quadriceps and the sternocleidomastoid muscles, coupled with a venous Indocyanine Green dye injection. Changes in WOB were significantly and positively related to changes in respiratory muscle blood flow (r = 0.73), whereby increasing the WOB increased blood flow. Conversely, changes in WOB were significantly and inversely related to changes in locomotor blood flow (r = 0.57), whereby decreasing the WOB increased locomotor blood flow. Oxygen uptake was not different during the control and resistor trials (3.8 ± 0.9 versus 3.7 ± 0.8 l min-1 , P > 0.05), but was lower on the proportional assist ventilator trial (3.4 ± 0.7 l min-1 , P < 0.05) compared with control. Our findings support the concept that respiratory muscle work significantly influences the distribution of blood flow to both respiratory and locomotor muscles.

Influence of inspiratory resistive loading on expiratory muscle fatigue in healthy humans.

NEW FINDINGS: What is the central question of this study? This study is the first to measure objectively both inspiratory and expiratory muscle fatigue after inspiratory resistive loading to determine whether the expiratory muscles are activated to the point of fatigue when specifically loading the inspiratory muscles. What is the main finding and its importance? The absence of abdominal muscle fatigue suggests that future studies attempting to understand the neural and circulatory consequences of diaphragm fatigue can use inspiratory resistive loading without considering the confounding effects of abdominal muscle fatigue. Expiratory resistive loading elicits inspiratory as well as expiratory muscle fatigue, suggesting parallel coactivation of the inspiratory muscles during expiration. It is unknown whether the expiratory muscles are likewise coactivated to the point of fatigue during inspiratory resistive loading (IRL). The purpose of this study was to determine whether IRL elicits expiratory as well as inspiratory muscle fatigue. Healthy male subjects (n = 9) underwent isocapnic IRL (60% maximal inspiratory pressure, 15 breaths min-1 , 0.7 inspiratory duty cycle) to task failure. Abdominal and diaphragm contractile function was assessed at baseline and at 3, 15 and 30 min post-IRL by measuring gastric twitch pressure (Pga,tw ) and transdiaphragmatic twitch pressure (Pdi,tw ) in response to potentiated magnetic stimulation of the thoracic and phrenic nerves, respectively. Fatigue was defined as a significant reduction from baseline in Pga,tw or Pdi,tw . Throughout IRL, there was a time-dependent increase in cardiac frequency and mean arterial blood pressure, suggesting activation of the respiratory muscle metaboreflex. The Pdi,tw was significantly lower than baseline (34.3 ± 9.6 cmH2 O) at 3 (23.2 ± 5.7 cmH2 O, P < 0.001), 15 (24.2 ± 5.1 cmH2 O, P < 0.001) and 30 min post-IRL (26.3 ± 6.0 cmH2 O, P < 0.001). The Pga,tw was not significantly different from baseline (37.6 ± 17.1 cmH2 O) at 3 (36.5 ± 14.6 cmH2 O), 15 (33.7 ± 12.4 cmH2 O) and 30 min post-IRL (32.9 ± 11.3 cmH2 O). Inspiratory resistive loading elicits objective evidence of diaphragm, but not abdominal, muscle fatigue. Agonist-antagonist interactions for the respiratory muscles appear to be more important during expiratory versus inspiratory loading.

Revisiting dysanapsis: sex-based differences in airways and the mechanics of breathing during exercise.

NEW FINDINGS: What is the topic of this review? This review focuses on sex-based differences in the anatomy of the respiratory system, which manifest in mechanical ventilatory constraints and potentially alter the integrative response to exercise. What advances does it highlight? Recent evidence indicates that women have smaller conducting airways than men, even when matched for lung size. Consequently, women are more likely to experience mechanical ventilatory constraints to exercise hyperpnoea. Furthermore, at a given ventilation, women have a higher work and oxygen cost of breathing, both of which may lead to differences in the whole-body integrative response to dynamic exercise. Our understanding of the human ventilatory response to exercise is largely based on a historical body of literature focused primarily on male rather than female research subjects. In recent years, important sex-based differences in the anatomy of the human respiratory system have been identified; for a given lung size, women appear to have smaller-diameter conducting airways than men. The presence of such inherent differences in the tracheobronchial tree greatly affects the mechanics of airflow generation, especially during conditions of high ventilation rates, such as exercise. Data from a growing number of studies suggest that women may be more susceptible to respiratory system limitations during exercise than their male counterparts. Specifically, women are more likely to experience expiratory flow limitation and exercise-induced arterial hypoxaemia and have a higher metabolic cost of breathing for a given ventilation. Collectively, the available evidence suggests that sex differences in the ventilatory response to exercise are present and may have important ramifications for the integrated response to exercise; however, several fundamental questions remain unanswered.

Oxygen cost of exercise hyperpnoea is greater in women compared with men.

KEY POINTS: The oxygen cost of breathing represents a significant fraction of total oxygen uptake during intense exercise. At a given ventilation, women have a greater work of breathing compared with men, and because work is linearly related to oxygen uptake we hypothesized that their oxygen cost of breathing would also be greater. For a given ventilation, women had a greater absolute oxygen cost of breathing, and this represented a greater fraction of total oxygen uptake. Regardless of sex, those who developed expiratory flow limitation had a greater oxygen cost of breathing at maximal exercise. The greater oxygen cost of breathing in women indicates that a greater fraction of total oxygen uptake (and possibly cardiac output) is directed to the respiratory muscles, which may influence blood flow distribution during exercise. ABSTRACT: We compared the oxygen cost of breathing (V̇O2 RM ) in healthy men and women over a wide range of exercise ventilations (V̇E). Eighteen subjects (nine women) completed 4 days of testing. First, a step-wise maximal cycle exercise test was completed for the assessment of spontaneous breathing patterns. Next, subjects were familiarized with the voluntary hyperpnoea protocol used to estimate V̇O2 RM . During the final two visits, subjects mimicked multiple times (four to six) the breathing patterns associated with five or six different exercise stages. Each trial lasted 5 min, and on-line pressure-volume and flow-volume loops were superimposed on target loops obtained during exercise to replicate the work of breathing accurately. At ∼55 l min(-1) V̇E, V̇O2 RM was significantly greater in women. At maximal ventilation, the absolute V̇O2 RM was not different (P > 0.05) between the sexes, but represented a significantly greater fraction of whole-body V̇O2 in women (13.8 ± 1.5 vs. 9.4 ± 1.1% V̇O2). During heavy exercise at 92 and 100% V̇O2max, the unit cost of V̇E was +0.7 and +1.1 ml O2 l(-1) greater in women (P < 0.05). At V̇O2max, men and women who developed expiratory flow limitation had a significantly greater V̇O2 RM than those who did not (435 ± 44 vs. 331 ± 30 ml O2  min(-1) ). In conclusion, women have a greater V̇O2 RM for a given V̇E, and this represents a greater fraction of whole-body V̇O2. The greater V̇O2 RM in women may have implications for the integrated physiological response to exercise.

Gas density alters expiratory time constants before and after experimental lung injury.

NEW FINDINGS: What is the central question of this study? Does the induction of a model of lung injury affect the expiratory time constant (τE) in terms of either total duration or morphology? Does ventilation with gases of different densities alter the duration or morphology of τE either before or after injury? What is the main finding and its importance? The use of sulfur hexafluoride in ventilating gas mixtures lengthens total expiratory time constants before and after lung injury compared with both nitrogen and helium mixtures. Sulfur hexafluoride mixtures also decrease the difference and variability of τE between fast- and slow-emptying compartments before and after injury when compared with nitrogen and helium mixtures. Acute lung injury is characterized by regional heterogeneity of lung resistance and elastance that may lead to regional heterogeneity of expiratory time constants (τE). We hypothesized that increasing airflow resistance by using inhaled sulfur hexafluoride (SF6) would lengthen time constants and decrease their heterogeneity in an experimental model of lung injury when compared with nitrogen or helium mixtures. To overcome the limitations of a single-compartment model, we employed a multisegment model of expiratory gas flow. An experimental model of lung injury was created using intratracheal injection of sodium polyacrylate in anaesthetized and mechanically ventilated female Yorkshire-cross pigs (n = 7). The animals were ventilated with 50% O2 and the remaining 50% as nitrogen (N2), helium (He) or sulfur hexafluoride (SF6). Values for τE decreased with injury and were more variable after injury than before (P < 0.001). Values for τE increased throughout expiration both before and after injury, and the rate of increase in τE was lessened by SF6 (P < 0.001 when compared with N2 both before and after injury). Altering the inhaled gas density did not affect indices of oxygenation, dead space or shunt. The use of SF6 in ventilating gas mixtures lengthens total expiratory time constants before and after lung injury compared with both N2 and He mixtures. Importantly, SF6 mixtures also decrease the difference and variability of τE between fast- and slow-emptying compartments before and after injury when compared with N2 and He mixtures.

Assessing neonatal heat balance and physiological strain in newborn infants nursed under radiant warmers in intensive care with fentanyl sedation.

PURPOSE: To assess heat balance status of newborn infants nursed under radiant warmers (RWs) during intensive care. METHODS: Heat balance, thermal status and primary indicators of physiological strain were concurrently measured in 14 newborns nursed under RWs for 105 min. Metabolic heat production (M), evaporative heat loss (E), convective (C) and conductive heat flow (K), rectal temperature (T re) and mean skin temperatures (T sk) were measured continuously. The rate of radiant heat required for heat balance (R req) and the rate of radiant heat provided (R prov) were derived. The rate of body heat storage (S) was calculated using a two-compartment model of 'core' (T re) and 'shell' (T sk) temperatures. RESULTS: Mean M, E, C and K were 10.5 ± 2.7 W, 5.8 ± 1.1 W, 6.2 ± 0.8 W and 0.1 ± 0.1 W, respectively. Mean R prov (1.7 ± 2.6 W) and R req (1.7 ± 2.7 W) were similar (p > 0.05). However, while the resultant mean change in body heat content after 105 min was negligible (-0.1 ± 3.7 kJ), acute time-dependent changes in S were evidenced by a mean positive heat storage component of +6.4 ± 2.6 kJ and a mean negative heat storage component of -6.5 ± 3.7 kJ. Accordingly, large fluctuations in both T re and T sk occurred that were actively induced by changes in RW output. Nonetheless, no active physiological responses (heart rate, breathing frequency and mean arterial pressure) to these bouts of heating and cooling were observed. CONCLUSIONS: RWs maintain net heat balance over a prolonged period, but actively induce acute bouts of heat imbalance that cause rapid changes in T re and T sk. Transient bouts of heat storage do not exacerbate physiological strain, but could in the longer term.

Do greater rates of body heat storage precede the accelerated reduction of self-paced exercise intensity in the heat?

AIM: To reevaluate the previous hypothesis that greater reductions in self-paced exercise intensity in the heat are mediated by early differences in the rate of body heat storage (S). METHODS: Eight trained volunteers cycled in 19 °C/1.8 kPa (COOL), 25 °C/1.2 kPa (NORM), and 34 °C/1.6 kPa (HOT), while maintaining an RPE of 16. Potential differences in S following the onset of exercise were assessed by comparing rates of esophageal temperature change (ΔT es/Δt); and estimated S values using a traditional two-compartment thermometric model (S therm) of changes in rectal (T re) and skin (T sk) temperature, and partitional calorimetry (S cal). RESULTS: After 15 min of exercise, workload decreased more in HOT vs. COOL (P = 0.03), resulting in a shorter time (HOT: 40.7 ± 14.9 min; COOL: 53.5 ± 18.7 min; P = 0.04) to 70 % of initial workload. However, there were no preceding differences in ΔT es/Δt between conditions (P = 0.18). S therm values were different between HOT and COOL during the first 5 min of exercise (P < 0.05), primarily due to negative S therm values (-32 ± 15 kJ min(-1)) in COOL, which according to partitional calorimetric measurements, required improbably high (~56 kJ min(-1)) rates of evaporation when no sweating on the back and thigh was observed until after 7.6 ± 1.5 min and 4.8 ± 1.7 min of exercise, respectively. S cal values in the first 5 min of exercise confirmed S was actually positive in COOL (+21 ± 8 kJ min(-1)) and not negative. Different S therm values following the onset of exercise at different environmental temperatures are simply due to transient differences in the rate of change in T sk. CONCLUSION: Reductions in self-paced exercise intensity in the heat are not mediated by early differences in S following the onset of exercise.

Dysanapsis is not associated with exertional dyspnoea in healthy male and female never-smokers aged 40 years and older.

In healthy adults, airway-to-lung (i.e., dysanapsis) ratio is lower and dyspnoea during exercise at a given minute ventilation (V̇E) is higher in females than in males. We investigated the relationship between dysanapsis and sex on exertional dyspnoea in healthy adults. We hypothesized that females would have a smaller airway-to-lung ratio than males and that exertional dyspnoea would be associated with airway-to-lung ratio in males and females. We analyzed data from n = 100 healthy never-smokers aged ≥40 years enrolled in the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who underwent pulmonary function testing, a chest computed tomography scan, and cardiopulmonary exercise testing. The luminal area of the trachea, right main bronchus, left main bronchus, right upper lobe, bronchus intermedius, left upper lobe, and left lower lobe were 22%-37% smaller (all p < 0.001) and the airway-to-lung ratio (i.e., average large conducting airway diameter relative to total lung capacity) was lower in females than in males (0.609 ± 0.070 vs. 0.674 ± 0.082; p < 0.001). During exercise, there was a significant effect of V̇E, sex, and their interaction on dyspnoea (all p < 0.05), indicating that dyspnoea increased as a function of V̇E to a greater extent in females than in males. However, after adjusting for age and total lung capacity, there were no significant associations between airway-to-lung ratio and measures of exertional dyspnoea, regardless of sex (all r < 0.34; all p > 0.05). Our findings suggest that sex differences in airway size do not contribute to sex differences in exertional dyspnoea.

Skin temperature over the carotid artery provides an accurate noninvasive estimation of core temperature in infants and young children during general anesthesia.

BACKGROUND: The accurate measurement of core temperature is an essential aspect of intraoperative management in children. Invasive measurement sites are accurate but carry some health risks and cannot be used in certain patients. An accurate form of noninvasive thermometry is therefore needed. Our aim was to develop, and subsequently validate, separate models for estimating core temperature using different skin temperatures with an individualized correction factor. METHODS: Forty-eight pediatric patients (0-36 months) undergoing elective surgery were separated into a modeling group (MG, n = 28) and validation group (VG, n = 20). Skin temperature was measured over the carotid artery (Tsk_carotid ), upper abdomen (Tsk_abd ), and axilla (Tsk_axilla ), while nasopharyngeal temperature (Tnaso ) was measured as a reference. RESULTS: In the MG, derived models for estimating Tnaso were: Tsk_carotid  + 0.52; Tsk_abd  + (0.076[body mass] + 0.02); and Tsk_axilla  + (0.081[body mass]-0.66). After adjusting raw Tsk_carotid, Tsk_abd , and Tsk_axilla values in the independent VG using these models, the mean bias (Predicted Tnaso - Actual Tnaso [with 95% confidence intervals]) was +0.03[+0.53, -0.50]°C, -0.05[+1.02, -1.07]°C, and -0.06[+1.21, -1.28°C], respectively. The percentage of values within ±0.5°C of Tnaso was 93.2%, 75.4%, and 66.1% for Tsk_carotid, Tsk_abd , and Tsk_axilla , respectively. Sensitivity and specificity for detecting hypothermia (Tnaso  < 36.0°C) was 0.88 and 0.91 for Tsk_carotid , 0.61 and 0.76 for Tsk_abd , and 0.91 and 0.73 for Tsk_axilla . Goodness-of-fit (R(2) ) relative to the line-of-identity was 0.74 (Tsk_carotid ), 0.34 (Tsk_abd ), and 0.15 (Tsk_axilla ). CONCLUSIONS: Skin temperature over the carotid artery, with a simple correction factor of +0.52°C, provides a viable noninvasive estimate of Tnaso in young children during elective surgery with a general anesthetic.

Effects of Face Masks on the Multiple Dimensions and Neurophysiological Mechanisms of Exertional Dyspnea.

INTRODUCTION: During the coronavirus disease 2019 pandemic, public health officials widely adopted the use of face masks (FM) to minimize infections. Despite consistent evidence that FMs increase dyspnea, no studies have examined the multidimensional components of dyspnea or their underlying physiological mechanisms. METHODS: In a randomized crossover design, 16 healthy individuals ( n = 9 women, 25 ± 3 yr) completed incremental cycling tests over three visits, where visits 2 and 3 were randomized to either surgical FM or no mask control. Dyspnea intensity and unpleasantness were assessed throughout exercise (0-10 Borg scale), and the Multidimensional Dyspnea Profile was administered immediately after exercise. Crural diaphragmatic EMG and esophageal pressure were measured using a catheter to estimate neural respiratory drive and respiratory muscle effort, respectively. RESULTS: Dyspnea unpleasantness was significantly greater with the FM at the highest equivalent submaximal work rate achieved by a given participant in both conditions (iso-work; 5.9 ± 1.7 vs 3.9 ± 2.9 Borg 0-10 units, P = 0.007) and at peak exercise (7.8 ± 2.1 vs 5.9 ± 3.4 Borg 0-10 units, P = 0.01) with no differences in dyspnea intensity ratings throughout exercise compared with control. There were significant increases in the sensory quality of "smothering/air hunger" ( P = 0.01) and the emotional response of "anxiousness" ( P = 0.04) in the FM condition. There were significant increases in diaphragmatic EMG and esophageal pressure at select submaximal work rates, but no differences in heart rate, pulse oximetry-derived arterial oxygen saturation, or breathing frequency throughout exercise with FMs compared with control. FMs significantly reduced peak work rate and exercise duration (both P = 0.02). CONCLUSIONS: FMs negatively impact the affective domain of dyspnea and increase neural respiratory drive and respiratory muscle effort during exercise, although the impact on other cardiorespiratory responses are minimal.

Perception of exercise-induced dyspnea after experimentally induced breathing discomfort.

The perception of dyspnea is influenced by both physiological and psychological factors. We sought to determine whether exertional dyspnea perception could be experimentally manipulated through prior exposure to heightened dyspnea while exercising. We hypothesized that dyspnea perception during exercise would be lower following an induced dyspnea task (IDT). Sixteen healthy participants (eight females, eight males) completed two days of exercise testing. Day 1 involved an incremental cycle exercise test starting at 40 W for females and 60 W for males, increasing by 20 W each minute until volitional exhaustion. Following the maximal exercise test on Day 1, participants completed IDT, involving 5 min of exercise at 70% of peak work rate with 500 mL dead space and external resistance (i.e., 6.8 ± 2.3 cm·H2O·s-1·L-1 inspiration, 3.8 ± 0.7 cm·H2O·s-1·L-1 expiration). Day 2 consisted of an incremental exercise test identical to Day 1. At maximal exercise, there were no differences in oxygen uptake (V̇O2; 44.7 ± 7.7 vs. 46.5 ± 6.3 mL·kg-1·min-1), minute ventilation (120 ± 35 vs. 127 ± 38 L·min-1), dyspnea (6.5 [4, 8.5] vs. 6 [4.25, 8.75]), or leg discomfort (6 [5, 8.75] vs. 7 [5, 9]) between days (all p > 0.05). At 60%-80% of peak V̇O2 (V̇O2peak), dyspnea was significantly lower on Day 2 (-0.75 [-1.375, 0] for 60% and -0.5 [0, -2] for 80%, p < 0.05) despite no differences in relevant physiological variables. The onset of perceived dyspnea occurred at a significantly higher exercise intensity on Day 2 than on Day 1 (42% ± 19% vs. 51% ± 17% V̇O2peak, respectively; p < 0.05). Except for 40% V̇O2peak (p = 0.05), RPE-L was not different at any intensities nor was the onset of perceived leg discomfort different between days (38% ± 14% vs. 43% ± 10% V̇O2peak, respectively; p = 0.10). Exposure to heightened dyspnea alters exercise-induced dyspnea perception during subsequent submaximal exercise bouts.

Sex, gender and the pulmonary physiology of exercise.

In this review, we detail how the pulmonary system's response to exercise is impacted by both sex and gender in healthy humans across the lifespan. First, the rationale for why sex and gender differences should be considered is explored, and then anatomical differences are highlighted, namely that females typically have smaller lungs and airways than males. Thereafter, we describe how these anatomical differences can impact functional aspects such as respiratory muscle energetics and activation, mechanical ventilatory constraints, diaphragm fatigue, and pulmonary gas exchange in healthy adults and children. Finally, we detail how gender can impact the pulmonary response to exercise.

Therapeutic hypothermia attenuates physiologic, histologic, and metabolomic markers of injury in a porcine model of acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a lung injury characterized by noncardiogenic pulmonary edema and hypoxic respiratory failure. The purpose of this study was to investigate the effects of therapeutic hypothermia on short-term experimental ARDS. Twenty adult female Yorkshire pigs were divided into four groups (n = 5 each): normothermic control (C), normothermic injured (I), hypothermic control (HC), and hypothermic injured (HI). Acute respiratory distress syndrome was induced experimentally via intrapulmonary injection of oleic acid. Target core temperature was achieved in the HI group within 1 h of injury induction. Cardiorespiratory, histologic, cytokine, and metabolomic data were collected on all animals prior to and following injury/sham. All data were collected for approximately 12 h from the beginning of the study until euthanasia. Therapeutic hypothermia reduced injury in the HI compared to the I group (histological injury score = 0.51 ± 0.18 vs. 0.76 ± 0.06; p = 0.02) with no change in gas exchange. All groups expressed distinct phenotypes, with a reduction in pro-inflammatory metabolites, an increase in anti-inflammatory metabolites, and a reduction in inflammatory cytokines observed in the HI group compared to the I group. Changes to respiratory system mechanics in the injured groups were due to increases in lung elastance (E) and resistance (R) (ΔE from pre-injury = 46 ± 14 cmH2 O L-1 , p < 0.0001; ΔR from pre-injury: 3 ± 2 cmH2 O L-1  s- , p = 0.30) rather than changes to the chest wall (ΔE from pre-injury: 0.7 ± 1.6 cmH2 O L-1 , p = 0.99; ΔR from pre-injury: 0.6 ± 0.1 cmH2 O L-1  s- , p = 0.01). Both control groups had no change in respiratory mechanics. In conclusion, therapeutic hypothermia can reduce markers of injury and inflammation associated with experimentally induced short-term ARDS.